Longitudinal and time-sequential studies have examined the dynamic interplay between the greater susceptibility to disruption and the greater capacity for reorganization and recovery (or sparing) of function of the immature nervous system. The functional outcome of these opposing processes was studied with respect to the model systems provided by the maturing hypothalamic-pituitary-adrenal axis and the hippocampus. Exposure to various toxicants was used to perturb these systems. Neonatal exposure to chlordecone, an organochlorine insecticide, produced imbalances in circulating and adrenal steroids as well as extremely rapid and apparently permanent changes in adrenal morphology. These alterations in the integrity of the hypothalamic-pituitary-adrenal axis were associated with long-term alterations in the sexual differentiation of hypothalamic nuclei, neurochemical alterations in catecholaminergic and serotonergic function, and selective memory deficits. Neonatal exposure to triethyl lead, the active metabolite of leaded gasoline, produced a preferential and permanent destruction of hippocampal pyramidal cell fields as indicated by quantitative neuromorphometry. This insult resulted in a permanent increase in behavioral reactivity independent of sensory modality, early undernutrition, and early testing effects. Pharmacological probes and receptor binding techniques linked this enhanced reactivity to a permanent dysfunction in cholinergic, but not dopaminergic, connections with the hippocampus proper. Initial studies which employed prenatal exposure to carbon monoxide, with carboxyhemoglobin levels within the range experienced by cigarette smokers, suggested a disruption of the hippocampus as indexed by an impairment in the acquisition and retention of a two-way avoidance task in juvenile aged offspring. While a substantial attenuation of these deficits was noted with muturation to adulthood, with continued aging there was a marked exaccerbation of learning and memory dysfunction.